Lung cancer and past occupational exposure to asbestos. Role of p53 and K-ras mutations

Am J Respir Cell Mol Biol. 1999 Apr;20(4):667-74. doi: 10.1165/ajrcmb.20.4.3404.


Studies on somatic mutations in lung cancers associated with cigarette smoking and asbestos exposure are few. We investigated prevalence of mutations in the p53 and K-ras genes in lung tumors from smokers with and without asbestos exposure at work. For K-ras mutations, the study was an extension of an earlier analysis. Nearly all of the 105 consecutive patients examined were smokers and had non-small-cell carcinoma of the lung with squamous-cell carcinoma or adenocarcinoma histology. Exposure to asbestos was estimated by pulmonary fiber counts and occupational histories. A pulmonary burden of >/= 1 x 10(6) asbestos fibers per gram of lung tissue, indicating work-related exposure, was found in 32% of the patients for whom fiber-analysis data were available (33 of 102 patients, all men). The statistical analysis showed pulmonary fiber count as the only significant predictor of adenocarcinoma histology, in contrast to squamous-cell carcinoma (smoking-adjusted odds ratio [OR] 3.0, 95% confidence interval [CI] 1.1 to 8.5). The frequency of p53 mutations was 39% (13 of 33) among the asbestos-exposed cases, as compared with 54% (29 of 54) among the nonexposed cases; the difference was not significant, however. In male ever-smokers, a long duration of smoking was associated with p53 mutation (OR 3.2, 95% CI 1.2 to 8.8). In adenocarcinoma, p53 mutations were less prevalent (10 of 30, 33%) as compared with squamous-cell carcinoma (28 of 46, 61%; P = 0.02), whereas a strong and significant association was found between adenocarcinoma and K-ras mutation (OR 37, 95% CI 5.8 to 232, adjusted for smoking and asbestos exposure). Asbestos exposure alone was not significantly associated with increased occurrence of K-ras mutations. In conclusion, the results may primarily reflect the observed excess of adenocarcinoma in the asbestos- exposed patients, and hence the decrease in p53 mutations and increase in K-ras mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / etiology
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adolescent
  • Age of Onset
  • Analysis of Variance
  • Asbestos*
  • Carcinoma, Non-Small-Cell Lung / etiology*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Genes, p53*
  • Genes, ras*
  • Humans
  • Lung / pathology
  • Lung / ultrastructure
  • Lung Neoplasms / etiology*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Mutation*
  • Occupational Exposure*
  • Regression Analysis
  • Smoking / genetics


  • Asbestos